Histamine is a biogenic amine involved in local immune responses as
well as regulating physiological function in the gut and acting as
a neurotransmitter.[1]
Histamine triggers the inflammatory
response. As part of an immune response to foreign pathogens, histamine is produced by basophils
and by mast cells found
in nearby connective tissues. Histamine increases the permeability
of the capillaries to white blood cells and other proteins, in
order to allow them to engage foreign invaders in the affected
tissues.[2] It is
found in virtually all animal body cells.

Histamine has two basic centres, namely the aliphaticamino group and
whichever nitrogen atom of
the imidazole ring does
not already have a proton.
Under physiological conditions, the aliphatic amino group (having a
pKa around 9.4) will
be protonated, whereas the second nitrogen of
the imidazole ring (pKa ≈ 5.8) will not be
protonated.[3]
Thus, histamine is normally protonated to a singly-charged cation.

Storage and
release

Mast cells.

Most histamine in the body is generated in granules in mast
cells or in white blood cells called basophils. Mast cells are
especially numerous at sites of potential injury - the nose, mouth,
and feet, internal body surfaces, and blood vessels. Non-mast cell
histamine is found in several tissues, including the brain, where it functions as a
neurotransmitter. Another important site of histamine storage and
release is the enterochromaffin-like (ECL)
cell of the stomach.

Roles in the
body

Advertisements

Sleep
regulation

Histamine is released as a neurotransmitter. The cell bodies of
neurons which release histamine are found in the posterior hypothalamus, in
various tuberomammillary nuclei. From
here, these histaminergic neurons project throughout the brain, to
the cortex through the medial forebrain bundle.
Histaminergic action is known to modulate sleep. Classically, antihistamines (H1 histamine
receptor antagonists) produce sleep. Likewise, destruction of
histamine releasing neurons, or inhibition of histamine synthesis
leads to an inability to maintain vigilance. Finally, H3 receptor antagonists
increase wakefulness.

It has been shown that histaminergic cells have the most
wakefulness-related firing pattern of any neuronal type thus far
recorded. They fire rapidly during waking, fire more slowly during
periods of relaxation/tiredness and completely stop firing during
REM and NREM (non-REM) sleep.
Histaminergic cells can be recorded firing just before an animal
shows signs of waking.

Suppressive
effects

While histamine has stimulatory effects upon neurons, it also
has suppressive ones that protects against the susceptibility to
convulsion, drug sensitization, denervation supersensitivity,
ischemic lesions and stress.[4] It has
also been suggested that histamine controls the mechanisms by which
memories and learning are forgotten.[5]

Erection and sexual
function

Libido loss and erectile failure can occur following histamine
(H2) antagonists such as cimetidine and ranitidine.[6]
The injection of histamine into the corpus cavernosum in men with
psychogenic impotence produces full or partial erections in 74% of
them.[7] It has
been suggested that H2 antagonists may cause sexual difficulties by
reducing the uptake of testosterone.[6]

Schizophrenia

Metabolites of histamine metabolite are increased in the
cerebrospinal fluid of schizophrenics while
the binding of H(1) receptor binding sites are decreased. Many
atypical antipsychotics have the effect of
increasing histamine turnover.[8]

Disorders

Nomenclature

"H substance" or "substance H" are occasionally used in medical
literature for histamine or a hypothetical histamine-like
diffusible substance released in allergic reactions of skin and in
the responses of tissue to inflammation.